title: Early markers of cognitive enhancement: developing an implicit measure of cognitive performance.
abstract: There is intense interest in the development of effective cognitive enhancing drugs which would have therapeutic application across a number of neurological and psychological disorders including dementia, schizophrenia and depression. However, development in this area has been limited by the absence of sensitive biomarkers which can be used to detect and refine therapeutic-like action in phase 1 clinical studies. The aim of the present study was therefore to develop a measure of cognition relevant to the action of candidate cognitive enhancers which might be sensitive to pharmacological manipulation in healthy volunteers. Healthy volunteers (n = 34) were randomised to receive a single dose of modafinil (100 mg) or placebo. Five hours post dose, attentional flexibility in learning was assessed using a novel implicit learning task. Volunteers also completed an auditory digit span task and visual analogue scales (VAS). Modafinil increased alertness as measured by the VAS. In the implicit learning task, modafinil enhanced learning rates in terms of both accuracy and reaction time, suggesting an increase in implicit rule learning. These results suggest that the novel learning task should be explored as a biomarker of early cognitive improvement which could be more sensitive than conventional measures.
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK, Abbie.pringle@psych.ox.ac.uk.
authors.forename: Abbie
authors.initials: A
authors.lastname: Pringle
authors.forename: Michael
authors.initials: M
authors.lastname: Browning
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Parsons
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007858:Learning / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D018697:Nootropic Agents / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D013647:Task Performance and Analysis; D064690:Wakefulness-Promoting Agents / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D018697:Nootropic Agents; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil